Pitolisant Effects on Alcohol Self-Administration in Heavy Drinkers
Study Details
Study Description
Brief Summary
This is a double-blind, randomized, placebo-controlled, crossover design trial that will test the effect of pitolisant on alcohol self-administration and craving following a priming dose of alcohol. The specific objective of this proposal is to determine whether pitolisant has effects on alcohol consumption and craving
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The present proposal is intended to answer the call for accelerating drug development by exploring the potential of a novel anticonvulsant, Pitolisant as a candidate medication for the treatment of AUD. Pitolisant is an H-3 receptor inverse agonist that is FDA-approved for treating narcolepsy which has been found to have effects of on alcohol craving and consumption in preclinical studies. The aims of this study are to test the effects of Pitolisant on alcohol self-administration and craving among a sample of non-treatment seeking heavy drinkers. The effects of 5-days of pitolisant (8.9mg) or placebo will be evaluated in a human laboratory using an alcohol self-administration methodology. In this within-subjects crossover design, heavy drinkers (N=28) will be randomized to the order of exposure (Pitolisant or placebo) prior to completing two alcohol self-administration trials. Subjects will receive a priming drink of alcohol and will have access to 8 alcoholic drinks over a 2-hour period. The investigators anticipate that subjects will consume less alcohol during an alcohol self-administration trial when receiving Pitolisant compared to when they are receiving placebo. Significant Pitolisant-induced reductions in the quantity of alcohol self-administered will be considered to be an indication that this drug may have value as an AUD medication. This study may provide a rationale for phase II clinical studies testing Pitolisant with a treatment-seeking AUD population.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pitolisant Subjects will take an 8.9 mg dose (two 4.45 mg pills) of pitolisant once per day on day 1 through 4. On day 5, 8.9 mg will be taken in front of staff prior to an alcohol self administration trial. |
Drug: Pitolisant
8.9mg Pitolisant for 5 days
Other Names:
|
| Placebo Comparator: Placebo Subjects will take an placebo once per day on day 1 through 4. On day 5, a placebo will be taken in front of staff prior to an alcohol self administration trial. |
Drug: Placebo
Inert ingredients
|
Outcome Measures
Primary Outcome Measures
- Alcohol Consumption [2.6 hours]
Alcohol consumption will be measured by using a graduated cylinder to determine the amount of alcohol given to the subject that was not consumed. This outcome will be measured as standard drink units. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
- Alcohol Craving [2.6 hours]
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving and the other end meaning intense alcohol craving. The Participant marks a point on the line that matches their amount of alcohol craving.
- Alcohol Urge [2.6 hours]
The Alcohol Urge questionnaire (AUQ) is an 8 item measure of self-reported urges to drink in human laboratory studies that assesses the participant's urge for an alcoholic drink at the time the questionnaire is completed, Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly disagree) and participants select the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. Lower scores are associated with less urge for an alcoholic drink.
Secondary Outcome Measures
- Alcohol-induced stimulation [2.6 hours]
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively.
- Alcohol craving during 4-day drug exposure [4 days]
The Visual Analog Scale (VAS) will be used to assess alcohol craving during the medication exposure period. The VAS is a 10 cm straight line with one end meaning no alcohol craving and the other end meaning intense alcohol craving. Higher scores are associated with more cravings.
- Alcohol consumption during the 4-day drug exposure [4 days]
Alcohol consumption during the 4 days of drug exposure will be measured using the timeline followback method
Eligibility Criteria
Criteria
Inclusion Criteria:
-
21-55 years of age
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Able to verify age with a state or federal picture identification
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Exceeds safe weekly drinking limits during the 28 days prior to consent (average of 14 drinks for women or 21 drinks for men per week)
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Reports at least one episode of binge drinking (>3 drinks for women, >4 drinks for men) in the 28 days prior consent.
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Meets DSM-5 criteria for mild alcohol use disorder or greater severity.
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Has a smartphone to complete medication exposure period study assessments.
Exclusion Criteria:
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Seeking treatment for alcohol problems
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Clinical Institute Withdrawal Assessment at ≥10
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DSM-5 diagnosis of current major depression, bipolar disorder, schizophrenia, bulimia/anorexia, dementia, insomnia disorder or a substance use disorder other than alcohol, nicotine, marijuana or caffeine
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If female, pregnant, nursing, have plans to become pregnant
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If female, does not agree to use an accepted form of birth control
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Has a medical contraindication to the use of pitolisant
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Has medical or mental condition for which further alcohol exposure at the planned dose range would be contraindicated
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Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes to the ideation question #4 of the C-SSRS)
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BMI is greater than 40 or less than 18
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Impaired renal function (GFR <80 mL/min)
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Have a history of any clinically significant renal or hepatic disease
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Child-Pugh Score equal to or greater than Class B (evaluated based on presence or absence of encephalopathy and ascites, INR, bilirubin, and albumin) [https://www.mdcalc.com/child-pugh-score-cirrhosis-mortality]
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Have a clinically significant ECG as determined by the investigator or abnormal ECG heart rate (<45 or >100 bpm) or QTc interval corrected for heart rate using the Fridericia formula (QTcF) > 450 msec
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Have a history of cardiac arrhythmias or who for other reasons are at risk for developing Torsade de Pointes including those with bradycardia, hypokalemia, and congenital QT interval prolongation
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Has received alcohol counseling or other non-pharmacologic intervention to treat AUD in the past 90 days
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Has taken medications that are used to treat AUD in the past 90 days
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Has urine toxicology results positive for cocaine, opioids, amphetamines, buprenorphine, methadone, methamphetamines, oxycontin, barbiturates, or benzodiazepines.
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Subject is taking a medication which will significantly alter drug metabolism (e.g., strong CYP2D6 inhibitors, strong CYP3A4 inducers, or H1 receptor antagonists that cross the blood barrier (e.g. diphenhydramine or meclizine).
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Subject is known to be a poor CYP2D6 metabolizer.
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Subject is unable to comfortably abstain from nicotine for a period of 8 hours.
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Has Chronic Obstructive Pulmonary Disease (COPD), history of solid organ transplant, sickle cell disease, severe heart disease or other health condition for which exposure to COVID-19 represents an unreasonable risk as determined by the study staff physician using accepted COVID-19 guidance (e.g. Centers for Disease Control, etc.).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston University Psychiatry Research Center, Clinical Studies Unit | Boston | Massachusetts | United States | 02118 |
Sponsors and Collaborators
- Boston Medical Center
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
- Principal Investigator: Eric Devine, PhD, Boston Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-40959
- 1R21AA028864-01